Phenolytic kinetic resolution of azido and alkoxy epoxides

ABSTRACT

Disclosed herein is a single step catalytic process for the production of enantiomerically pure α-Aryloxy-α′-Azido/Alkoxy alcohols of formula (A). The invention, in particular discloses phenolytic kinetic resolution of racemic anti and syn azido/alkoxy epoxides to generate two stereocentres of high optical purities of formula (A).

The following specifications particularly describe the nature of theinvention and the manner in which it is to be performed:

TECHNICAL FIELD OF INVENTION

The present invention relates to a single step catalytic process for theproduction of enantiomerically pure α-Aryloxy-α′-Azido/Alkoxy alcoholsof formula (A). The invention in particular, relates to PhenolyticKinetic Resolution of racemic anti and syn azido/alkoxy epoxides togenerate two stereocentres of high optical purities of formula (A).

Wherein X is selected from N₃ and OBn;

-   ‘R’ is selected independently from hydrogen, alkyl (C₁-C₅), alkenyls    (C₂-C₆), alkynyls (C₂-C₆), aryl, alkoxy, cyano, halo, nitro,    —C(O)—R₁, —CO₂R₂, hydroxyl, —NH(R₃), cycloalkyl, cycloalkenyl,    thiols, thiocarbonyl, sulfonyl or a heterocycle(C₃-C₅), where R₁, R₂    and R₃ represent hydrogen, alkyl(C₁-C₅).-   Y denotes tert-butyldimethylsilyloxide (TBSO) or phenyl; and-   ‘a’ and ‘b’ denote syn or anti position.

BACKGROUND AND PRIOR ART

Enantiopure mono hydroxyl syn or anti azido/alkoxy-1,2-diols arevaluable building blocks for the bioactive pharmaceuticals. It is aknown fact that enantiomerically pure drugs have numerous advantagesover racemic drug mixtures including advantages, such as, fewer sideeffects and greater potency, which result in part from the ability ofliving systems to differentiate between enantiomeric compounds. Accessto these building blocks is provided by several routes includingasymmetric reduction of aryloxy ketones or the ring opening ofenantiopure terminal epoxides.

Ring opening of terminal epoxides in presence of a chiral catalyst knownin the art are used to resolve single epoxide.

An article titled “Asymmetric Processes Catalyzed by Chiral (Salen)Metal Complexes” by Jay F. Larrow and Eric N. Jacobsen in TopicsOrganomet Chem (2004) 6: 123-152 relate to catalytic asymmetric ringopening or kinetic resolution of meso and racemic terminal epoxidesusing variety of synthetically useful nucleophiles to obtain enantiopuredissymmetrically substituted epoxides. The catalyst is selected fromchiral (salen)Co(III) and Cr(III) complexes. An article titled“Asymmetric Catalytic Synthesis of α-Aryloxy Alcohols: KineticResolution of Terminal Epoxides via Highly Enantioselective Ring-Openingwith Phenols by Joseph M. Ready and Eric N. Jacobsen in J. Am. Chem.Soc. 1999,121, 6086-6087 relates to phenolytic kinetic resolution ofterminal epoxides in presence of (salen)Co(III) catalyst to generate1-aryloxy-2-alcohols.

The aforementioned kinetic resolution technique, however, results inα-aryloxy alcohol with only one stereo centre.

Further, the processes described in the art to synthesize functionalizedα-Aryloxy alcohols involve higher temperature conditions andprotection/deprotection of various functional groups leading tomultistep reaction sequences thereby limiting the overall yield and theenantioselectivity of the process particularly unsuitable for the atomeconomic synthesis.

In context with the growing demand for enantiopure α-azido/alkoxyalcohols as intermediate in preparation of enantiomeric pure drugs andto expand the scope of stereoselective ring opening of racemic terminalepoxides, present inventors have explored the possibility of improvingupon the existing kinetic resolution technique to provide enantiopureα-Aryloxy-α′-Azido/Alkoxy alcohols with two stereocentres.

The previous work published by the applicant in the article titled“Co(III)(salen)-catalyzed HKR of two stereocentered alkoxy- and azidoepoxides: a concise enantioselective synthesis of (S,S)-reboxetine and(+)-epi-cytoxazone” by R. Santhosh Reddy, Pandurang V. Chouthaiwale et.al in Chem. Commun., 2010, 46, 5012-5014 discloses hydrolytic kineticresolution (HKR) of racemic syn- or anti- alkoxy- and azido epoxidescatalyzed by Co(salen) complex to obtain enantioenriched syn- or anti-alkoxy- and azido epoxides and the corresponding 1,2-diols.

The present inventors have observed that synthesis of certain bioactivemolecules is still difficult using the previously known kineticresolution technique with water as nucleophile. Moreover, selectiveprotection of alcohols is generally tedious which may increase thenumber of steps in the preparation of bio active products.

In view of the above, there remains a need to provide an economicalprocess that can provide monohydroxy protected syn or antiazido/alkoxy-1,2-diols as valuable “building blocks” for the bioactivepharmaceuticals.

OBJECT OF THE INVENTION

The main objective of the present invention is to provide a single stepcatalytic process for the production of enantiomerically pureα-Aryloxy-α′-Azido/Alkoxy alcohols of formula (A).

Another objective of the present invention is to provide PhenolyticKinetic Resolution of racemic anti and syn azido/alkoxy epoxides togenerate two stereocentres of high optical purities of formula A.

Another objective of the present invention is to provide a process forasymmetric synthesis of antihypertensive agentICI118,551((2S,3S)-1-(2,3-dihydro-4-methyl-1H-inden-7-yloxy)-3-(isopropylamino)butan-2-ol)from intermediate (17).

SUMMARY OF THE INVENTION

Accordingly, the present invention provides a single step process forthe synthesis of α-Aryloxy-α′-Azido/Alkoxy alcohols of general formula Awith two stereocenters by phenolytic kinetic resolution,

-   -   wherein X is selected from N₃ and OBn;    -   ‘R’ is selected independently from hydrogen, alkyl (C₁-C₅),        alkenyls (C₂-C₆), alkynyls (C₂-C6), aryl, alkoxy, cyano, halo,        nitro, —C(O)—R₁, —CO₂R₂, hydroxyl, —NH(R₃), cycloalkyl,        cycloalkenyl, thiols, thiocarbonyl, sulfonyl or a        heterocycle(C₃-C₅), where R₁, R₂ and R₃ represent hydrogen,        alkyl(C₁-C₅).    -   Y denotes TBSO or phenyl; and    -   ‘a’ and ‘b’ denote syn or anti position    -   Wherein the said process comprising the steps of;    -   (a) adding racemic epoxide of formula (1),

to phenol of formula (2)

wherein, X, Y and R are as defined above,

-   at room temperature ranging between 25-35° C. to preformed (salen)    Co (III) catalyst of formula 3,

followed by addition of tertiary butyl methyl ether, stirring and addingpyridinium p-toluene sulfonate, filtering, concentrating, followed bypurifying to obtain the α-Aryloxy-α′-Azido/Alkoxy alcohols of generalformula A.

In an embodiment of the invention, the anti α-Aryloxy-α′-Azido/Alkoxyalcohols, is represented by formula 4;

In one embodiment of the invention, the syn α-Aryloxy-α′-Azido/Alkoxyalcohols is, represented by formula 7;

In another embodiment of the invention, the α-Aryloxy-α′-Azido/Alkoxyalcohols of formula 4 and 7 comprises;

In yet another embodiment, the yield of α-Aryloxy-α′-Azido/Alkoxyalcohols of general formula A is in the range of 35-98%

In still another embodiment, enantiomeric excess (ee) % ofα-Aryloxy-α′-Azido/Alkoxy alcohols of general formula A is in the rangeof 94-99%

In still another embodiment, a process for asymmetric synthesis ofantihypertensive agentICI118,551((2S,3S)-1-(2,3-dihydro-4-methyl-1H-inden-7-yloxy)-3-(isopropylamino)butan-2-ol)

from intermediate (17)

(2S,3S)-1-(2,3-dihydro-4-methyl-1H-inden-7-yloxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol (17) comprising;

-   i. reducing intermediate (17) obtained from the process of claim 1    in the presence of Pd/C in lower alcohol;-   ii. protecting the amino group with isopropyl chloride in presence    of a base and halogenated hydrocarbon as solvent;-   iii. deprotecting the terminal alcohol group with Camphorsulfonic    Acid (CSA)    (2S,3S)-4-(2,3-dihydro-4-methyl-1H-inden-7-yloxy)-2-(isopropylamino)butane-1,3-diol)    in lower alcohol at room temperature ranging between 25-35° C.;-   iv. reacting the product of step (iii) with p-TsCl    (p-Toluenesulfonyl chloride) in presence of a base and halogenated    hydrocarbon as solvent at temperature ranging between 0° C. to 25°    C.; and-   v. reducing the compound of step (iv) with LiAlH₄ in THF at reflux    to obtain antihypertensive agent ICI118.

In still another embodiment, lower alcohol used in step (i) and (iii) isselected from the group consisting of methanol or ethanol.

In still another embodiment, base used in step (ii) and (iv) is selectedfrom the group consisting of ethylamine, triethylamine or pyridine.

In still another embodiment, halogenated solvent used in step (ii) and(iv) is selected from the group consisting of chloroform, carbontetrachloride or Dichloromethane.

DESCRIPTION OF THE INVENTION

The invention will now be described in detail in connection with certainpreferred and optional embodiments, so that various aspects thereof maybe more fully understood and appreciated.

The present invention relates to efficient catalytic route to obtainenantiomerically pure α-aryloxy-α′-Azido/Alkoxy alcohols, which arevaluable building blocks for bioactive pharmaceuticals, from anti andsyn azido/alkoxy racemic epoxides.

The present invention relates to a single step process for the synthesisof α-Aryloxy-α′-Azido/Alkoxy alcohols of formula A with twostereocenters by phenolic kinetic resolution,

Wherein X is selected from N₃ and OBn;

-   ‘R’ is selected independently from hydrogen, alkyl (C₁-C₅), alkenyls    (C₂-C₆), alkynyls (C₂-C₆), aryl, alkoxy, cyano, halo, nitro,    —C(O)—R₁, —CO₂R₂, hydroxyl, —NH(R₃), cycloalkyl, cycloalkenyl,    thiols, thiocarbonyl, sulfonyl or a heterocycle(C₃-C₅), where R₁, R₂    and R₃ represent hydrogen, alkyl(C₁-C₅).-   Y denotes TBSO or phenyl; and-   ‘a’ and ‘b’ denote syn or anti position-   Wherein the said process consists of comprising;-   adding racemic epoxide of formula 1,

-   to phenol of formula 2

-   wherein, X, Y, and R are as defined above,-   at room temperature to preformed (salen) Co (III) catalyst (formula    3),

followed by addition of tertiary butyl methyl ether, stirring and addingpyridinium p-toluene sulfonate, filtering, concentrating, followed bypurifying to obtain the desired enantiopure product.

The catalyst for the reaction is prepared by oxidizing commerciallyavailable Co (II) salen complex with (CF₃)₃COH in the solvent for 45-50min, stirring followed by removing the solvent by rotary evaporation toobtain Co (III) salen catalyst (formula 3).

In an aspect, the present invention provides phenolytic kineticresolution of anti-azido/alkoxy epoxides. The process is schematicallygiven below:

In an aspect, the products of phenolytic kinetic resolution ofanti-azido epoxides of the current invention are given below in Table 1:

TABLE 1 Phenolytic kinetic resolution of anti-azido epoxides of thepresent invention % Sr. Substrate Scope Yield^(a) ee No. 2 Product 4 of4 (%)^(b) 1

  (2S,3S)-3-azido-4-(tert-butyl-dimethyl siloxy)-1- phenoxybutan-2-ol 6595 2

  (2S,3S)-1-(p-tolyloxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 72 97 3

  (2S,3S)-1-(m-tolyloxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 70 98 4

  (2S,3 S)-1-(o-tolyloxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 35 96 5

  (2S,3S)-1-(4-tert-butylphenoxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 76 99 6

  (2S,3S)-1-(3-methoxyphenoxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 60 98 7

  4-((2S,3S)-(3-azido-4-(tert-butyl-dimethyl siloxy)-2-hydroxybutoxy)benzonitrile 87 96 8

  (2S,3S)-1-(4-nitrophenoxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 84 98 9

  (2S,3S)-1-(4-fluorophenoxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 72 99 10

  (2S,3S)-1-(4-bromophenoxy)-3-azido-4-(tert-butyl-dimethyl siloxy)butan-2-ol 86 97 11

  (2S,3S)-1-(4-chlorophenoxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 90 96 12

  (2S,3S)-1-(3,5-diehlorophenoxy)-3-azido-4-tert-butyl- dimethylsiloxy)butan-2-ol 89 95 13

  1-(4-(2S,3S)-(3-azido-4-(tert-butyl-dimethyl siloxy)-2-hydroxybutoxy)phenyl)ethanone 88 99 14

  4-((2S,3S)-(3-azido-4-tert-butyl-dimethyl siloxy)-2-hydroxybutoxy)benzaldehyde 95 96 15

  2-(2S,3S)-(3-azido-4-(tert-butyl-dimethyl siloxy)-2-hydroxybutoxy)-5-bromobenzaldehyde 58 97 16

  methyl 4-((2S,3S)-(3- azido-4-(tert-butyl-dimethyl siloxy)-2-hydroxybutoxy)benzoate 96 95 17

  (2S,3S)-1-(2,3-dihydro-4-methyl-1H-inden-7-yloxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 75 99 ^(a)Isolated yield after column chromatographicpurification with respect to phenol (2). ^(b)ee enantiomeric excessdetermined by chiral HPLC analysis.

In yet another aspect, the products of phenolytic kinetic resolution ofanti-alkoxy epoxides of the current invention are given below in Table2:

TABLE 2 Phenolytic kinetic resolution of anti-alkoxy epoxides of presentinvention % Sr. Substrate Scope Yield^(a) ee No. 2 Product 4 of 4(%)^(b) 1

  4-((2R,3S)-4-(tert-butyl dimethylsiloxy)-3-(benzyloxy)-2-hydroxybutoxy)benzonitrile 87 98 2

  (2R,3S)-4-(tert-butyl dimethylsiloxy)-1-(4-nitrophenoxy)-3-(benzyloxy)butan-2-ol 89 96 3

  1-(4-((2R,3S)-4-(tert-butyl dimethylsiloxy)-3-(benzyloxy)-2-hydroxybutoxy)phenyl)ethanone 98 98 4

  4-((2R,3S)-4-(tert-butyl dimethylsiloxy)-3-(benzyloxy)-2-hydroxybutoxy)benzaldehyde 75 99 5

  methyl 4-((2R,3S)-4-(tert-butyl dimethylsiloxy)-3-(benzyloxy)-2-hydroxybutoxy)benzoate 81 97 6

  (2R,3S)-1-(2,4,5-trichlorophenoxy)-4-(tert-butyldimethylsiloxy)-3-(benzyloxy)butan-2-ol 87 98 ^(a)Isolated yield aftercolumn chromatographic purification with respect to phenol (2). ^(b)eeenantiomeric excess determined by chiral HPLC analysis.

In another aspect, the present invention provides a phenolytic kineticresolution of syn-azido/alkoxy epoxides which is schematically givenbelow:

In another aspect, the products of phenolytic kinetic resolution ofsyn-azido epoxides of the current invention are given below in Table 3:

TABLE 3 Phenolytic kinetic resolution of syn-azido epoxides of presentinvention Sr. Substrate Product % Yield^(a) ee No. 2 7 of 7 (%)^(b) 1

  1-(4-((2S,3R)-3-azido-2-hydroxy-3- phenylpropoxy)phenyl)ethanone 93 982

  methyl 4-((2S,3R)-3-azido-2-hydroxy-3- phenylpropoxy)benzoate 95 99 3

  (1R,2S)-3-(4-nitrophenoxy)-1-azido-1- phenylpropan-2-ol 96 96^(a)Isolated yield after column chromatographic purification withrespect to phenol (2). ^(b)ee enantiomeric excess determined by chiralHPLC analysis.

In yet another aspect, the products of phenolytic kinetic resolution ofsyn-alkoxy epoxides of the current invention are given below in Table 4:

TABLE 4 Phenolytic kinetic resolution of syn-alkoxy epoxides of presentinvention Sr. Substrate % Yield^(a) of ee No. 2 Product 7 7 (%)^(b) 1

  1-(4-((2R,3R)-3-(benzyloxy)-2-hydroxy-3- phenylpropoxy)phenyl)ethanone89 97 ^(a)Isolated yield after column chromatographic purification withrespect to phenol (2). ^(b)ee enantiomeric excess determined by chiralHPLC analysis.

In another aspect, the present invention provides asymmetric synthesisof antihypertensive agent ICI118,551 from compound of formula (17) asgiven below:

The Asymmetric synthesis of antihypertensive agent ICI118,551((2S,3S)-1-(2,3-dihydro-4-methyl-1H-inden-7-yloxy)-3-(isopropylamino)butan-2-ol)from intermediate (17) comprises;

-   i. Reducing intermediate (17) obtained from the process of claim 1    in presence of Pd/C in lower alcohol;-   ii. Protecting the amino group with isopropyl chloride in presence    of a base and halogenated hydrocarbon as solvent;-   iii. Deprotecting the terminal alcohol group with CSA in lower    alcohol at room temperature; and-   iv. Reacting the product of step (iii) with p-TsCl in presence of a    base and halogenated hydrocarbon as solvent at 0° C.; and-   v. Reducing the compound of step (iv) with LiAlH₄ in THF at reflux    to obtain the desired product.

The base is selected from methylamine, ethylamine, triethylamine,pyridine etc. The halogenated hydrocarbons are selected from chloroform,carbon tetrachloride, etc. The lower alcohols are selected from C₁-C₆alcohols.

The phenolytic kinetic resolution provides atom economic synthesis ofα-Aryloxy-α′-Azido/Alkoxy alcohols of high optical purity in high yield.

INDUSTRIAL ADVANTAGES

-   -   The applicant sates that the kinetic resolution technique        published in Chem Comm. (disclosed above in the article) limits        itself to the use of only water as the nucleophile for the        production of two-chiral centered resolution products (synlanti        azido/alkoxy diols and epoxides). In the present work, however,        any phenol can be employed as nucleophile, for the first time,        in the two-chiral centered resolution process for effective        Phenolytic Kinetic Resolution of syn/anti azido/alkoxy epoxides,        which indeed resulted in products (syn/anti α-Aryloxy        α′-azido/alkoxy alcohols) with high enantiomeric excess and        yields.    -   The products (syn/anti α-Aryloxy-α′-azido/alkoxy alcohols)        obtained in the present work after Phenolytic Kinetic Resolution        are entirely different from products obtained in the publication        in Chem Comm (synlanti azido/alkoxy diols and epoxides).    -   With the present method, less number of steps (atom economy) is        involved to make certain bioactive compounds; otherwise it        requires multi-steps leading to low yields and % ee of the final        products.    -   Selective protection of diols is generally tedious but the        present method provides a simple procedure to produce        mono-protected diols as aryl ethers.    -   Bioactive molecules which are difficult to synthesize using        previous method can now be synthesized easily using present        method for e.g. ICI-118,551.    -   The yields obtained in present method are excellent up to 99%        based on phenol as compared to 48% reported in the Chem Comm        paper.

The following examples are given by way of illustration and thereforeshould not be construed to limit the scope of the present invention

EXAMPLE General Experimental Procedure for Phenolytic Kinetic ResolutionPreparation of Catalyst

Commercially available (salen) Co(II) complex (0.302 g, 0.500 mmol) waseffectively oxidized to (salen) Co(III) complex (3) simply by stirringit with (CF₃)₃COH (1.180 g, 5.00 mmol) in CH₂Cl₂ (5.0 mL) open to theatmosphere for 45 min and then removing the solvent by rotaryevaporation.

General Procedure for the Phenolytic Kinetic Resolutions of Syn and AntiAzido/Alkoxy Epoxide (Scheme 1 and 2)

A 10 mL flask was charged with 86 mg (0.100 mmol) of catalyst (3) and100 mg MS 3 Å. Epoxide (5.00 mmol) (1) or (6) and phenol (2.25 mmol) (2)were added at room temperature, followed by addition of TBME (0.15 mL).The reaction was stirred at room temperature until complete conversionof phenol, at which time 75 mg (0.30 mmol) pyridinium p-toluenesulfonatewas added. The reaction mixture was filtered through a pad of silica andwashed with 50% EtOAc/hexanes. The filtrate was concentrated andpurified by chromatography on silica gel with EtOAc/hexanes. Theenantiomeric purity was determined by GC or HPLC.

Spectral Studies of the Products 1. Compound of(2S,3S)-3-azido-4-(tert-butyl-dimethyl siloxy)-1-phenoxybutan-2-ol 1(Table 1)

Yield: 65%; gum; IR (CHCl₃, cm⁻¹): 690, 752, 837, 1042, 1108, 1243,1497, 1599, 2099, 2857, 2929, 2953, 3460; ¹H NMR (200 MHz, CDCl₃) δ 012(s, 6H), 0.93 (s, 9H), 2.67 (d, J=5.02 Hz, 1H), 4.03 (m, 5H), 6.93 (m,3H), 7.31 (m, 2H) 2H); ¹³C NMR (50 MHz, CDCl₃): −5.59, 18.18, 25.78,63.44, 63.74, 69.59, 68.99, 114.54, 121.35, 129.51, 158.21; Anal. Calcd.for C₁₆H₂₇N₃O₃Si requires C, 56.94; H, 8.06; N, 12.45%. found C, 56.92;H, 8.04; N, 12.43%.

2. Compound of (2S,3S)-1-(p-tolyloxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 2 (Table 1)

Yield: 72%; gum; IR (CHCl₃, cm⁻¹): 777, 838, 1047, 1109, 1172, 1258,1289, 1462, 1490, 1586, 1603, 2098, 2857, 2284, 2929, 2953, 3451; ¹H NMR(200 MHz, CDCl₃) δ 0.12 (s, 6H), 0.92 (s, 9H), 2.29 (s, 1H), 2.67 (d,J=4.987 Hz, 1H) 3.56 (m, 1H), 4.00 (dm, 5H), 6.8. (d, J=8.58 Hz, 2H),7.06 (d, J=8.49 Hz, 2H); ¹³C NMR (50 MHz, CDCl₃): 21-5.53, 18.25, 20.52,25.84, 63.55, 63.82, 69.82, 69.24, 69.65, 11.49, 130, 130.56, 156.20;Anal. Calcd. for C₁₇H₂₉N₃O₃Si requires C, 57.92; H, 8.58; N, 11.92%.found C, 57.90; H, 8.56; N, 11.90%.

3. Compound of 4-((2S,3S)-(3-azido-4-(tert-butyl-dimethylsiloxy)-2-hydroxybutoxy)benzonitrile 7 (table 1)

Yield: 87%; gum; IR (CHCl₃, cm⁻¹): 778, 836, 1031, 1111, 1172, 1257,1463, 1471, 1509, 1609, 2099, 2226, 2857 2929, 2953, 2445; ¹H NMR (200MHz, CDCl₃) δ 0.012 (s, 6H), 0.92 (s, 9H), 2.70 (d, J=4.93 Hz, 1H 1H),3.50 (m, 1H), 4.03 (m, 1H), 4.03 (m, 5H), 6.98 (d, J=9.13 Hz, 2H), 7.59(d, J=8.77 Hz, 2H); ¹³C NMR (50 MHz, CDCl3): −5.58, 18.18, 25.77, 63.14,63.62, 69.55, 69.62, 115.30, 133.98, 161.80; Anal. Calcd. forC₁₇H₂₆N₄O₃Si requires C, 56.17; H, 7.49; N, 15.41%. found C, 56.15; H,7.47; N, 15.39%.

4. Compound of(2S,3S)-1-(4-chlorophenoxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol11 (Table 1)

Yield: 90 gum; IR (CHCl₃, cm⁻¹): 778, 837, 1095, 1243, 1492, 2100, 2858,2929, 2953, 3446; ¹H NMR (200 MHz, CDCl3) δ 0.12 (s, 6H), 0.93 (s, 9H),2.66 (d, J=4.67, 1H), 3.59 (m, 1H), 4.02 (m, 5H), 6.85 (d, J=8.95 Hz,2H), 7.44 (d, J=8.86 Hz, 2H); ¹³C NMR (50 MHz, CDCl₃): −5.59, 18.18,25.77, 63.70, 63.25, 69.47, 69.62, 115.81, 126.35, 129.40, 156.83; Anal.Calcd. for C₁₆H₂₆C1N₃O₃Si requires C, 51.53; H, 7.30; N, 11.27%. foundC, 51.50; H, 7.28; N, 11.25%.

5. Compound of methyl4-((2S,3S)-(3-azido-4-(tert-butyl-dimethylsiloxy)-2-hydroxybutoxy)benzoate16 (Table 1)

Yield: 81%; gum; IR (CHCl₃, cm⁻¹): 771, 839, 1112, 1170, 1254, 1283,1436, 1511, 1606, 1716, 2099, 2857, 2930, 3471; ¹H NMR (200 MHz, CDCl₃)δ 0.13 (s, 6H), 0.93 (s, 9H), 2.73 (d, J=5.05 Hz, 1H), 3.61 (m, 1H),3.89 (s, 1H), 4.01 (m, 3H), 4.17 (m, 2H), 6.94 (d, J=9.00 Hz, 2H), 7.88(d, J=9.00 Hz, 2H); ¹³C NMR (50 MHz, CDCl₃): −5.57, 18.20, 25.79, 51.88,63.28, 63.71, 69.34, 69.69 114.13, 123.19, 131.67, 162, 166.61; Anal.Calcd. for C₁₈H₂₉N₃O₅Si requires C, 54.52; H, 7.63; N, 10.60%. found C,54.50; H, 7.61; N, 10.58%.

6. Compound of(2S,3S)-1-(3-methoxyphenoxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol6 (Table 1)

Yield: 60%; gum; IR (CHCl₃, cm⁻¹): 771, 839, 1112, 1170, 1254, 1283,1436, 1511, 1606, 1716, 2099, 2857, 2930, 3471; ¹H NMR (200 MHz, CDCl₃)δ 0.12 (s, 6H), 0.93 (s, 9H), 2.67-2.68 (dd, J=3.05 Hz, 1H), 3.97 (m,1H), 3.78 (s, 1H), 4.2-4.06 (m, 3H), 4.09-4.17 (dd, J=3.36, 9.50, 1H),6.46-6.51 (m, 2H), 7.19 (t, 1H); ¹³C NMR (50 MHz, CDCl₃): −5.23, 18.55,26.15, 55.48, 63.79, 64.09, 70.00, 101.54, 107.05, 107.36, 130.327,159.84, 161.24; Anal. Calcd. for C₁₇H₂₉N₃O₄Si requires C, 55.56; H,7.95; N, 11.43%. found C, 55.25; H, 7.85; N, 11.35%.

7. Compound of(2S,3S)-1-(3,5-dichlorophenoxy)-3-azido-4-tert-butyldimethyl)butan-2-ol12 (Table 1)

Yield: 89%; gum; IR (CHCl₃, cm⁻¹): 771, 839, 1112, 1170, 1254, 1283,1436, 1511, 1606, 1716, 2099, 2857, 2930, 3471; ¹H NMR (200 MHz, CDCl₃)δ 0.12 (s, 6H), 0.92 (s, 9H), 2.73-2.75 (d, J=5.56 Hz, 1H), 3.57-3.66(m, 1H), 3.88-4.20 (m, 5H), 6.85-6.90 (d, J=8.82 Hz, 1H), 7.16-7.21 (dd,J=2.53, 8.80 Hz, 1H), 7.36-7.37 (d, J=2.53, 1H); ¹³C NMR (50 MHz,CDCl₃): −5.50, 18.26, 25.85, 51.88, 63.39, 63.82, 69.43, 70.81, 114.65,124.06, 126.75, 130.11, 152.68; Anal. Calcd. for C₁₆H₂₅Cl₂N₃O₃Sirequires C, 47.29; H, 6.20; N, 10.34%. found C, 47.18; H, 6.09; N,10.40%.

8. Compound of2-(2S,3S)-(3-azido-4-(tert-butyl-dimethylsiloxy)-2-hydroxybutoxy)-5-bromobenzaldehyde15 (Table 1)

Yield: 58%; gum; IR (CHCl₃, cm⁻¹): 771, 839, 1112, 1170, 1254, 1283,1436, 1511, 1606, 1716, 2099, 2857, 2930, 3471; ¹H NMR (200 MHz, CDCl3)δ 0.13 (s, 6H), 0.92 (s, 9H), 3.56-3.64 (m, 1H), 3.90-4.10 (m, 3H),4.16-4.29 (m, 2H), 6.90 (d, J=8.81 Hz, 1H), 7.60-7.66 (dd, J=2.61, 8.87Hz, 1H), 7.87-7.88 (d, J=2.50, 1H), 10.28 (s, 1H); ¹³C NMR (50 MHz,CDCl₃): −6.18, 17.58, 25.16, 62.67, 63.06, 68.87, 70.00, 113.45, 114.46,125.69, 131.78, 137.75, 158.76, 187.68; Anal. Calcd. for C₁₇H₂₆BrN₃O₄Sirequires C, 45.95; H, 5.90; N, 9.46%. found C, 45.90; H, 5.95; N, 9.48%.

9. Compound of1-(4-(2S,3S)-(3-azido-4-(tert-butyl-dimethylsiloxy)-2-hydroxybutoxy)phenyl)ethanone13 (Table 1)

Yield: 88%; gum; IR (CHCl₃, cm⁻¹): 777, 836, 1033, 1114, 1173, 1256,1307, 1600, 2098, 2857, 2929, 2953, 3440; ¹H NMR (200 MHz, CDCl₃) δ 0.13(s, 6H), 0.93 (s, 9H), 2.56 (s, 3H), 2.73-2.76 (d, J=4.97 Hz, 1H),3.55-3.67 (m, 1H), 3.894.24 (m, 5H), 6.93-6.98 (d, J=8.89 Hz, 2H),7.91-7.95 (d, J=8.94 Hz, 2H); ¹³C NMR (50 MHz, CDCl₃): −5.58, 18.18,25.78, 26.20, 63.40, 63.66, 69.47, 114.22, 130.62, 130.85, 162.27,196.64; Anal. Calcd. for C₁₈H₂₉N₃O₄Si requires C, 56.96; H, 7.70; N,11.07%. found C, 56.92; H, 7.65; N, 11.02%.

10. Compound of(2S,3S)-1-(4-bromophenoxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol10 (Table 1)

Yield: 86%; gum; IR (CHCl₃, cm⁻¹): 778, 837, 1003, 1072, 1103, 1242,1488, 2099, 2857, 2929, 2953, 3461; ¹H NMR (200 MHz, CDCl₃) δ 0.12 (s,6H), 0.93 (s, 9H), 2.67-2.69 (d, J=4.73 Hz, 1H), 3.53-3.61 (m, 1H),3.87-4.12 (m, 5H), 6.78-6.82 (m, 2H), 7.36-7.40 (m, 2H); ¹³C NMR (50MHz, CDCl₃): −5.573, 18.22, 25.82, 63.28, 63.714, 69.66, 113.67, 116.36,132.40, 157.39; Anal. Calcd. for C₁₆H₂₆BrN₃O₃Si requires C, 46.15; H,6.29; N, 10.09%. found C, 46.10; H, 6.28; N, 10.05%.

11. Compound of(2S,3S)-1-(4-nitrophenoxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 8 (Table 1)

Yield: 87%; gum; IR (CHCl₃, cm⁻¹): 779, 840, 862, 1111, 1260, 1298,1343, 1498, 1514, 1593, 1608, 2100, 2857, 2929, 2954, 3461; ¹H NMR (200MHz, CDCl₃) δ 0.13 (s, 6H), 0.93 (s, 9H), 2.72-2.75 (d, J=4.86 Hz, 1H),3.56-3.65 (m, 1H), 3.91-4.07 (m, 3H), 4.13-4.28 (m, 2H), 6.98-7.03 (d,J=9.35 Hz, 2H), 8.20-8.24 (d, J=9.31 Hz, 2H); ¹³C NMR (50 MHz, CDCl₃):−5.56, 18.21, 25.79, 63.14, 63.66, 69.67, 70.09, 114.59, 125.92, 141.89,163.35; Anal. Calcd. for C₁₆H₂₆N₄O₅Si requires C, 50.24; H, 6.85; N,14.65%. found C, 50.22; H, 6.87; N, 14.68%.

12. Compound of(2S,3S)-1-(4-fluorophenoxy)-3-azido-4-(tert-butyldimethylsiloxy)butan-2-ol9 (Table 1)

Yield: 72%; gum; IR (CHCl₃, cm⁻¹): 778, 836, 1098, 1220, 1252, 1507,2100, 2858, 2930, 2953, 3440; ¹H NMR (200 MHz, CDCl₃) δ 0.12 (s, 6H),0.93 (s, 9H), 2.67-2.70 (d, J 5.08 Hz, 1H), 3.53-3.62 (m, 1H), 3.87-4.11(m, 5H), 6.82-6.89 (m, 2H), 6.94-6.98 (m, 2H); ¹³C NMR (50 MHz, CDCl3):−5.54, 18.24, 25.82, 63.39, 63.77, 69.69, 115.58, 115.74, 116.20,154.39, 155.23; Anal. Calcd. for C₁₆H₂₆FN₃O₃Si requires C, 54.06; H,7.37; N, 11.82%. found C, 54.08; H, 7.35; N, 11.81%.

13. Compound of(2S,3S)-1-(m-tolyloxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 3(Table 1)

Yield: 70%; gum; IR (CHCl₃, cm⁻¹): 774, 838, 1109, 1172, 1258, 1289,1462, 1500, 1603, 2098, 2857, 2884, 2929, 2953, 3451; NMR (200 MHz,CDCl₃) δ 0.12 (s, 6H), 0.93 (s, 9H), 2.33 (s, 3H), 2.65-2.68 (d, J=4.84Hz, 1H), 3.53-3.62 (m, 1H), 3.87-4.13 (m, 5H), 6.69-6.80 (m, 3H),7.12-7.20 (m, 1H); ¹³C NMR (50 MHz, CDCl₃): −5.52, 18.25, 21.53, 25.85,63.55, 63.80, 69.02, 69.63 111.56, 115.43, 122.25, 129.30, 139.51,158.30; Anal. Calcd. for C₁₇H₂₉N₃O₃Si requires C, 58.09; H, 8.32; N,11.95%. found C, 58.11; H, 8.35; N, 11.85%.

14. Compound of(2S,3S)-1-(o-tolyloxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol 4(Table 1)

Yield: 35%; gum; IR (CHCl₃, cm⁻¹): 774, 838, 1109, 1172, 1258, 1289,1462, 1500, 1603, 2098, 2857, 2884, 2929, 2953, 3451; ¹H NMR (200 MHz,CDCl₃) δ 0.12 (s, 6H), 0.93 (s, 9H), 2.24 (s, 3H), 2.63-2.65 (d, J=5.36Hz, 1H), 3.57-3.65 (m, 1H), 3.88-3.95 (m, 3H), 4.02-4.13 (m, 2H),6.81-6.91 (m, 2H), 7.11-7.15 (m, 2H); ¹³C NMR (50 MHz, CDCl₃): −5.58,16.23, 18.19, 25.78, 29.67, 63.57, 63.82, 68.99, 69.75, 111.25, 121.11,126.54, 126.90, 130.79, 156.52; Anal. Calcd. for C₁₇H₂₉N₃O₃Si requiresC, 58.09; H, 8.32; N, 11.95%. found C, 58.02; H, 8.35; N, 11.98%.

15. Compound of(2S,3S)-1-(4-tert-butylphenoxy)-3-azido-4-(tert-butyldimethylsiloxy)butan-2-ol5 (Table 1)

Yield: 76%; gum; IR (CHCl₃, cm⁻¹): 777, 836, 1113, 1243, 1513, 2095,2858, 2929, 2956, 3460; ¹H NMR (200 MHz, CDCl₃) δ 0.12 (s, 6H), 0.92 (s,9H), 1.30 (s, 9H), 2.65-2.68 (d, 5.24 Hz, 1H), 3.53-3.62 (m, 1H),3.80-4.14 (m, 5H), 6.82-6.86 (m, 2H), 7.27-7.31 (m, 2H); ¹³C NMR (50MHz, CDCl₃): −5.48, 18.28, 25.88, 31.60, 34.16, 63.50, 63.86, 69.12,69.68, 114.15, 126.35, 144.10, 156.05; Anal. Calcd. for C₂₀H₃₅N₃O₃Sirequires C, 61.03; H, 8.96; N, 10.68%. found C, 61.08; H, 8.92; N,10.63%.

16. Compound of4-((2S,3S)-(3-azido-4-tert-butyldimethylsiloxy)-2-hydroxybutoxy)benzaldehyde14 (Table 1)

Yield: 95%; gum; IR (CHCl₃, cm⁻¹): 778, 836, 1110, 1167, 1258, 1509,1578, 1601, 1689, 2099, 2857, 2884, 2929, 3440; ¹H NMR (200 MHz, CDCl₃)δ 0.123 (s, 6H), 0.93 (s, 9H), 2.77-2.80 (d, J=5.06 Hz, 1H), 3.56-3.65(m, 1H), 3.95-4.06 (m, 3H), 4.16-4.27 (m, 2H), 7.01-7.05 (m, 2H),7.82-7.87 (m, 2H), 9.89 (s, 1H); ¹³C NMR (50 MHz, CDCl₃): −5.53, 18.22,25.82, 63.31, 63.69, 69.61, 114.88, 130.39, 132.04, 163.34, 190.61;Anal. Calcd. for C₁₇H₂₇N₃O₄Si requires C, 55.86; H, 7.45; N, 11.50%.found C, 55.90; H, 7.46; N, 11.53%.

17. Compound of (1R,2S)-3-(4-nitrophenoxy)-1-azido-1-phenylpropan-2-ol 3(table 3):

Yield: 90%; gum; IR (CHCl₃, cm⁻¹): 702, 752, 845, 1111, 1167, 1260,1342, 1510, 1592, 2105, 3481; ¹H NMR (200 MHz, CDCl3) δ 2.63-2.65 (d,0.1=4.26, 1H), 3.80-3.87 (dd, 4.83, 9.80 Hz, 1H), 4.00-4.17 (m, 2H),4.78-4.82 (d, J=7.30 Hz, 1H), 6.88-6.92 (m, 2H), 7.35-7.41 (m, 5H),8.16-8.20 (m, 2H); ¹³C NMR (50 MHz, CDCl₃): 67.83, 68.83, 73.18, 114.47,125.83, 132.04, 127.47, 129.12, 135.80, 141.88, 163.15; Anal. Calcd. forC₁₅H₁₄N₄O₄ requires C, 57.32; H, 4.49; N, 17.83%. found C, 57.28; H,4.44; N, 17.82%.

18. Compound of1-(4-((2S,3R)-3-azido-2-hydroxy-3-phenylpropoxy)phenyl)ethanone 1 (table3)

Yield: 88%; gum; IR (CHCl₃, cm⁻¹): 775, 845, 1110, 1173, 1254, 1359,1599, 1671, 2104, 3426; ¹H NMR (200 MHz, CDCl₃) δ 2.54 (s, 3H),2.65-2.67 (d, J=4.63, 1H), 3.77-3.84 (dd, J=4.80, 9.7 Hz, 1H), 3.96-4.13(m, 2H), 4.79-4.82 (d, J=7.38 Hz, 1H), 6.84-6.88 (m, 2H), 7.32-7.41 (m,5H), 7.87-7.92 (m, 2H); ¹³C NMR (50 MHz, CDCl₃): 26.25, 67.81, 68.42,73.30, 114.17, 127.52, 128.89, 129.00, 130.59, 136.14, 162.16, 196.73;Anal. Calcd. for C₁₇H₁₇N₃O₃ requires C, 65.58; H, 5.50; N, 13.50%. foundC, 65.54; H, 5.48; N, 13.48%.

19. Compound of1-(4-((2R,3S)-4-(tert-butyldimethylsiloxy)-3-(benzyloxy)-2-hydroxybutoxy)phenyl)ethanone3 (Table 2)

Yield: 98% white solid mp: 91-92° C.; IR (CHCl₃, cm⁻¹): 699.28, 775.75,957.19, 1093.07, 1258.78, 1359.27, 1470.93, 1575.75, 1600.40, 1671.94,2856.59, 2928.76, 3473.28; ¹H NMR (200 MHz, CDCl₃) δ 0.09 (S, 6H), 0.92(s, 9H), 2056 (s, 3H), 2.90 (sb 1H), 3.66 (m, 1H), 3.88 (dd, j=2.17 Hz,2H), 4.14 (m, 3H), 4.68 (dd, J=11.62 Hz, 2H), 6.90 (m, 2H), 7.27 (m,5H), 7.92 (m, 2H); ¹³C NMR (50 MHz, CDCl₃): −5.42, 18.28, 25.93, 26.33,63.27, 69.20, 71.04, 72.81, 78.42, 114.26, 127.90, 128.00, 128.45,130.57, 137.97, 162.63, 196.45; Anal. Calcd. for C₂₅H₃₆O₅Si requires C,67.53; H, 8.16. found C, 67.49; H, 8.16.

20. Compound of methyl4-((2R,3S)-4-(tert-butyldimethylsiloxy)-3-(benzyloxy)-2-hydroxybutoxy)benzoate5 (Table 2)

Yield: 81% colorless liquid; IR (CHCl₃, cm⁻¹): 771.58, 837.64, 1169.55,1255.29, 1435.72, 1511.62, 1605.92, 1718.16, 2928.78, 3478.36; ¹H NMR(200 MHz, CDCl₃) 80.09 (s, 6H), 0.91 (s, 9H), 2.94 (sb, 1H), 3.63 (m,1H), 3.91 (m, 5H), 4.12 (m, 3H), 4.68 (dd, J=11.6 Hz, 2H), 6.92 (dt,J=2.81 Hz, 2H), 7.27 (m, 5H), 7.98 (dt, J=2.71 Hz, 2H); ¹³C NMR (50 HZ,CDCl₃): −5.40, 18.29, 25.94, 51.84, 63.28, 69.15, 70.94, 72.82, 78.51,114.17, 122.81, 128.02, 128.44, 131.61, 138.0, 162.46, 166.70; Anal.Calcd. for C₂₅H₃₆O₆Si requires C, 65.19; H, 7.88. found C, 65.18; H,7.86.

21. Compound of4-((2R,3S)-4-(tert-butyldimethylsiloxy)-3-(benzyloxy)-2-hydroxybutoxy)benzonitrile1 (Table 2)

Yield: 87% colorless solid, mp: 62-63° C.; IR (CHCl₃, cm⁻¹): 778.43,835.46, 1096.18, 1172.50, 1258.45, 1302.46, 1454.96, 1508.86, 1605.60,2224.99, 2856.83, 2883.40, 2929.04, 2953.53, 3474.10; ¹H NMR (200 MHz,CDCl₃) δ 0.09 (s, 6H), 0.91 (s, 9H), 2.92 (m, 1H), 3.64 (m, 1H), 3.86(s, 1H), 3.89 (d, J=Hz, 1H), 4.11 (m, 3H), 4.56 (d, J=HZ, 1H), 4.67 (d,J=Hz, 1H), 6.95 (dt, J=Hz, 2H), 7.27 (m, 5H), 7.59 (dt, J=2.65 Hz, 2H);¹³C NMR (50 HZ, CDCl₃): −5.55, 18.13, 25.78, 62.97, 69.31, 72.59, 78.28,104.04, 115.18, 118.83, 127.75, 127.8, 128.29, 133.74, 137.79, 161.97;Anal. Calcd. for C₂₄H₃₃NO₄Si requires C, 67.41; H, 7.78; N 3.28. foundC, 67.42; H, 7.80.

22. Compound of4-((2R,3S)-4-(tert-butyldimethylsiloxy)-3-(benzyloxy)-2-hydroxybutoxy)benzaldehyde4 (Table 2)

Yield: 75%; gum; IR (neat, cm⁻¹): 755, 834, 1097, 1256, 1462, 1509,1600, 1693, 2928, 3454; ¹H-NMR (200 MHz, CDCl₃): δ 0.09 (s, 6H), 0.92(s, 9H), 2.95 (br s, 1H), 3.65 (m, 1H) 3.88 (m, 2H), 4.14 (m, 3H), 4.68(dd, j=11.62 Hz, 2H), 7.00 (m, 2H), 7.84 (m, 2H), 9.88 (s, 1H); ¹³C-NMR(50 MHz, CDCl₃): δ −542, 18.27, 25.92, 63.21, 69.35, 71.04, 72.78,78.32, 114.86, 128, 128.45, 130.16, 131.16, 131.94, 137.91, 163.74,190.49; Anal. Calcd. for C₂₄H₃₄O₅Si: C, 66.94; H, 7.96; 0, 18.58; Si,6.52. Found: C, 66.91; H, 7.95; O, 18.56; Si, 6.51%.

23. Compound of(2R,3S)-1-(2,4,5-trichlorophenoxy)-4-(tert-butyldimethylsiloxy)-3-(benzyloxy)butan-2-ol6 (Table 2)

Yield: 78%; gum; IR (neat, cm⁻¹): 701, 763, 1050, 1261, 1454, 1492,2104, 2935, 3034, 3416; ¹H-NMR (200 MHz, CDCl3): δ 0.09 (s, 6H), 0.92(s, 9H), 2.90 (s, 1H), 3.68 (m, 1H) 4.03 (m, 5H), 4.69 (m, 2H), 6.93 (s,1H), 7.28 (m, 5H), 7.43 (s, 1H); ¹³C-NMR (50 MHz, CDCl3): δ −540, 18.30,25.94, 63.42, 70.62, 70.89, 72.91, 78.23, 115.03, 122.101, 124.39,127.90, 128.46, 130.80, 131.26, 137.97, 153.35; Anal. Calcd. forC₂₃H₃₁Cl₃O₄Si: C, 54.60; H, 6.18; Cl, 21.02; O, 12.65; Si, 5.55. Found:C, 54.58; H, 6.15; Cl, 21.01; O, 12.62; Si, 5.51;%.

24. Compound of(2R,3S)-4-(tert-butyldimethylsiloxy)-1-(4-nitrophenoxy)-3-(benzyloxy)butan-2-ol2 (Table 2)

Yield: 89%; colorless liquid; IR (neat, cm⁻¹): 752, 778, 1111, 1263,1340, 1517, 1593, 2856, 2928, 3472; ¹H-NMR (200 MHz, CDCl₃): δ 0.10 (s,6H), 0.92 (s, 9H), 2.97 (br s, 1H), 3.62 (m, 1H) 3.90 (m, 2H), 4.15 (m,3H), 4.68 (dd, j=11.68 Hz, 2H), 6.94 (m, 2H), 7.29 (m, 5H), 8.20 (m,2H); ¹³C-NMR (50 MHz, CDCl₃): δ −548, 18.22, 25.86, 63.05, 69.80, 71.02,72.68, 78.11, 114.49, 125.77, 127.96, 128.42, 137.78, 141.61, 163.70;Anal. Calcd. for C₂₃H₃₃NO₆Si: C, 61.72; H, 7.43; N, 3013; 0, 21.45; Si,6.27. Found: C, 61.70; H, 7.42; N, 3.13; O, 21.44; Si, 6.25;%.

25. Compound of1-(4-((2R,3R)-3-(benzyloxy)-2-hydroxy-3-phenylpropoxy)phenyl)ethanone 1(Table 4)

Yield: 89%; gum; IR (neat, cm⁻¹): 701, 755, 1065, 1255, 1358, 1454,1599, 1673, 3453; ¹H-NMR (200 MHz, CDCl₃): δ 2.54 (s, 3H), 3.04 (br s,1H), 3.80 (m, 1H) 4.05 (m, 2H), 4.51 (m, 3H), 6.84 (m, 2H), 7.34 (m,9H), 7.86 (m, 2H); ¹³C-NMR (50 MHz, CDCl₃): δ 26.23, 68.00, 70.86,73.95, 81.48, 114.17, 127.48, 127.89, 127.98, 128.45, 128.56, 128.75,130.46, 137.50, 137.82, 162.42, 196.27; Anal. Calcd. for C₂₄H₂₄O₄: C,76.57; H, 6.43; O, 17.00%. Found: C, 76.56; H, 6.41; O, 17.01%.

The invention claimed is:
 1. A single step process for the synthesis ofα-Aryloxy-α′-Azido/Alkoxy alcohols of general formula A with twostereocenters by phenolic kinetic resolution,

wherein X is selected from N₃ and O-benzyl (OBn); ‘R’ is selectedindependently from hydrogen, alkyl (C₁-C₅), alkenyls (C₂-C₆), alkynyls(C₂-C₆), aryl, alkoxy, cyano, halo, nitro, —C(O)—R₁, —CO₂R₂, hydroxyl,—NH(R₃), cycloalkyl, cycloalkenyl, thiols, thiocarbonyl, sulfonyl or aheterocycle(C3-C₅), where R₁, R₂ and R₃ represent hydrogen,alkyl(C₁-C₅); Y denotes O-tert-butyldimethylsilyl (OTBS) or phenyl; and‘a’ and ‘b’ denote syn or anti position; wherein the said processcomprising the steps of: (a) adding racemic epoxide of formula (1),

to phenol of formula (2)

wherein, X, Y and R are as defined above, at room temperature rangingbetween 25-35° C. to preformed (salen) Co (III) catalyst of formula 3,

followed by addition of tertiary butyl methyl ether, stirring and addingpyridinium p-toluene sulfonate, filtering, concentrating, followed bypurifying to obtain the α-Aryloxy-α′-Azido/Alkoxy alcohols of generalformula A.
 2. The process according to claim 1, wherein the antiα-Aryloxy-α′-Azido/Alkoxy alcohols, is represented by formula 4;


3. The process according to claim 1, wherein the synα-Aryloxy-α′-Azido/Alkoxy alcohols is, represented by formula 7;


4. The process according to claims 2 and 3, wherein theα-Aryloxy-α′-Azido/Alkoxy alcohols of formula 4 and 7 comprises:


5. The process as claimed in claim 1 wherein the yield ofα-Aryloxy-α′-Azido/Alkoxy alcohols of general formula A is in the rangeof 35-98%.
 6. The process as claimed in claim 1 wherein enantiomericexcess (ee) % of α-Aryloxy-α′-Azido/Alkoxy alcohols of general formula Ais in the range of 94-99%.
 7. Asymmetric synthesis of antihypertensiveagentICI118,551((2S,3S)-1-(2,3-dihydro-4-methyl-1H-inden-7-yloxy)-3-(isopropylamino)butan-2-ol)

from intermediate (17)

(2S,3S)-1-(2,3-dihydro-4-methyl-1H-inden-7-yloxy)-3-azido-4-(tert-butyl-dimethylsiloxy)butan-2-ol (17) comprising; i. reducing intermediate (17)obtained from the process of claim 1 in the presence Of Pd/C in loweralcohol; ii. protecting the amino group with isopropyl chloride inpresence of a base and halogenated hydrocarbon as solvent; iii.deprotecting the terminal alcohol group with CSA(2S,3S)-4-(2,3-dihydro-4-methyl-1H-inden-7-yloxy)-2-(isopropylamino)butane-1,3-diol)in lower alcohol at room temperature ranging between 25-35° C.; iv.reacting the product of step (iii) with p-TsCl (p-Toluenesulfonylchloride) in presence of a base and halogenated hydrocarbon as solventat temperature ranging between 0° C. to 25° C.; and v. reducing thecompound of step (iv) with LiAlH₄ in THF at reflux to obtainantihypertensive agent ICI118,.
 8. A process as claimed in claim 7,wherein lower alcohol used in step (i) and (iii) is selected from thegroup consisting of methanol or ethanol.
 9. A process as claimed inclaim 7, wherein base used in step (ii) and (iv) is selected from thegroup consisting of ethylamine, triethylamine or pyridine.
 10. A processas claimed in claim 7, wherein halogenated solvent used in step (ii) and(iv) is selected from the group consisting of chloroform, carbontetrachloride or Dichloromethane.